The Genetic Neuroepidemiology and Biostatistics team at the Barcelonaβeta Brain Research Center (BBRC), a research center of the Pasqual Maragall Foundation, has characterized the genetic predisposition to Alzheimer's and other neurological disorders in cognitively healthy people in the preclinical stages of the disease, that is, when there are still no obvious symptoms but there are already changes in the brain and biomarkers associated with the degenerative process. Although genetics are only a direct cause of Alzheimer's in 1% cases, characterizing the genetic predisposition will open the doors to more personalized medical care and prevention, and will allow for better selection of participants for specific clinical studies based on their genetic profile. In this sense, the Dr. Natalia Vilor-Tejedor, senior researcher of the study and team leader, highlights that “This characterization allows us to obtain a more complete profile of the study participants, and thus facilitate the development of personalized preventive strategies, a better selection of participants for clinical trials and prediction of response to treatment.”.
The research, published in the scientific journal Alzheimer's & Dementia: The Journal of the Alzheimer's Association, is based on data from the Alfa cohort, promoted by the “la Caixa” Foundation and made up of more than 2,700 participants without cognitive alterations, and also includes data from the Alzheimer's Disease Neuroimaging Initiative (ADNI). The results of this investigation, according to Patricia Genius, team researcher and also author of the study, “They will improve the accuracy of the conclusions of epidemiological studies, and open the door to a better understanding of the biological pathways associated with neurodegenerative processes.”.
Genetic predisposition measures beyond the APOE gene
Although genetics are only a direct cause of Alzheimer's in a very small percentage of cases (around 1%), the genetic predisposition to develop the disease may have an impact on processes of cognitive decline or brain atrophy that could precede the development of symptoms. In addition, people with a high genetic predisposition could be more susceptible to the effect of other risk factors, such as environmental exposures, causing an acceleration of cognitive decline or even brain atrophy. The APOE gene is the main genetic risk factor for Alzheimer's, but there are other variables.Knowing in detail the non-modifiable factors, such as the genetic predisposition to the disease, allows us to identify the people most vulnerable to risk, and take action on the modifiable risk factors.", Vilor-Tejedor points out.
In this regard, the team has calculated polygenic risk scores (PRS) for Alzheimer's and other neurological disorders, risk factors associated with Alzheimer's disease and aging processes. PRS are measures that estimate a person's genetic predisposition to develop a disease. from the weighted sum of the effect of the genetic variants associated with this disease in previous studies.
“The results will allow us to decipher how the genetic predisposition to Alzheimer's interacts with other risk factors. to influence the development of the disease and the processes prior to the appearance of symptoms”, explains the researcher. “It will also allow a better characterization of the mechanisms that influence these biological processes.”.
More than 2,500 participants in the Alpha cohort
The team analyzed these data in 2,527 participants of the Alfa study, a longitudinal project that follows healthy people between 45 and 75 years old, mostly descendants of people with Alzheimer's, to study cognitive, biological and neuroimaging changes related to aging and Alzheimer's. The genetic predisposition to Alzheimer's has been characterized among these BBRC participants and those of the ADNI clinical groups, an international consortium that includes healthy people with mild cognitive decline or Alzheimer's dementia.
The research team found that BBRC participants, especially those with amyloid protein alterations, exhibit a distribution of genetic predisposition to Alzheimer's similar to that of clinical groups, further characterizing the Alpha cohort for studying early pathological changes in Alzheimer's.Alpha is one of the few cohorts in the world with such extensive characterization“, says Vilor-Tejedor. “We knew it was a cohort enriched in Alzheimer's risk factors, but with this new study We have gone a step further by adding a new dimension of biological variables, which will allow for even more precise prevention studies", concludes the researcher.
Bibliographic reference:
Vilor-Tejedor, N., Genius, P., Rodríguez-Fernández, B., et al. 'Genetic characterization of the ALFA study: Uncovering genetic profiles in the Alzheimer's continuum'. Alzheimer's & Dementia. DOI: 10.1002/alz.13537
